Arrest of human gastric cancer AGS cells by tangeretin via CyclinB1 upregulation and inhibition of ERK phosphorylation

Aim: To study the effects of tangeretin on proliferation and cell cycle of human AGS gastric cancer cells and its mechanisms. Methods: MTT assay was used to detect the growth inhibition rates of human AGS gastric cancer cells treated with tangeretin. The cell cycle distribution was measured by flow cytometry. The protein expressions of Cyclin B1, Cyclin D1, Cyclin E1, ERK and p-ERK were detected by western blot. Results: MTT assay showed tangeretin inhibited the growth of AGS gastric cancer cells in a time- and dose-dependent manner (P < 0.01). Tangeretin arrested AGS cells in S phase compared with control group for 24 h (P < 0.01). After treatment with tangeretin for 48 h and 72 h, AGS cells were arrested in G2/M phase (P <0.05, P <0.0l). Western blot showed that tangeretin increased the expression of Cyclin B1 protein in a dose-dependent manner (P < 0.05, P < 0.01), but had no effects on that of Cyclin D1 and Cyclin E1. ERK was not changed and p-ERK was downregulated after treatment with tangeretin (P < 0.01). Conclusion: Tangeretin can inhibit proliferation of human AGS gastric cancer cells and induce cell cycle arrest in S and G2/M phases. The inhibition of ERK phosphorylation and upregulation of Cyclin B1 protein might be one of the mechanisms.